Sasa Ivanovic

Ivermectin effects on motor coordination and contractions of isolated rat diaphragm.

Ivermectin, the antiparasitic drug from the macrocyclic lactones class raises attention due to its high efficiency against nematodes and arthropods and very specific toxic and side effects that it may produce in host. Dominant clinical symptoms of adverse effects and toxicity of ivermectin in animals are tremor, ataxia, CNS depression and coma which often results in mortality. In our study increasing intravenous doses of ivermectin, (6 or more times higher than therapeutic dose: 1.25, 2.5, 3.75, 5.0, 6.25 and 7.5 mg/kg), caused dose-dependent disturbance of motor coordination in treated rats. The median effective dose (ED50) that was able to impair the rota-rod performance in rats treated 3 min before testing was 2.52 mg/kg. This effect weakens over time, while in the rats treated 60 min before the rota-rod test, ED50 of ivermectin was 4.21 mg/kg. Whereas, all tested doses of ivermectin did not cause any other clinical symptoms of toxicity. Ivermectin has no effect on the contractions of isolated diaphragm caused by the EFS, which effectively blocked mecamylamine (100 μM) and pancuronium (1 and 2 μM). Effect on motor coordination is the first detectable clinical symptom of ivermectin toxicity and apparently is a result of its central effects.

The application of adsorbent bentonite in oxidative stress induced by paraquat

The protective effect of bentonite (natural and synthetic) in oxidative stress induced by paraquat was studied on 32 adult male Wistar rats. The animals were divided into four groups (n=8). The first group received only paraquat p.o. (via a gastric tube). An hour after administration of paraquat, the second and the third group were treated with natural and synthetic bentonite, respectively, while the fourth group was untreated (control). All three experimental groups were treated once a day, throughout 8 consecutive days. Blood samples were taken 0, 1, 4, 6 and 8 days after the beginning of the treatment. Oxidative stress induced by paraquat was estimated by means of catalase activity (CAT - mmol/H2O2/min/g Hb) and malondialdehyde quantity (MDA - nmol/g Hb). Oxidative stress proved to be significant an hour and 192 hours after the beginning of chronic intoxication by paraquat. Both natural and synthetic bentonite expressed a protective action from oxidative stress in the period from 24 h to 144 h post application, acting through the external capacity of cationic exchange, which is known to be approximately 10%. The absorption of paraquat depends on the size of the molecule and its polarisation and is performed by the mechanisms of ion exchange (ionic and electrostatic interaction). Nevertheless, both absorbents developed a significant protective effect (approximately 50 %) 1 h and 192 h after the first application of paraquat, indicating that these protectors act as molecular sieves and thus suppress the process of lipid peroxidation and the development of even more intensive oxidative stress.

Downregulation of nicotinic and muscarinic receptor function in rats after subchronic exposure to diazinon

Highlights • We studied the development of tolerance to subchronic p.o. administration of DZN in rats, under both in vivo and in vitro conditions• As a consequence of AChE inhibition, ACh neurotransmitters are being accumulated in over stimulated nicotinic and muscarinic receptors.• With isolated diaphragm and ileum, we examined the down regulation of nicotinic and muscarinic receptor function through EFS technique.• The results of our research could be useful in forensic diagnostics of organophosphate poisoning.

Density functional theory calculation of lipophilicity for organophosphate type pesticides

Density functional method with continuum solvation model is used for calculation of partition coefficient log K OW and determination of lipophilicity of 22 most frequently used organophosphate type pesticides. Excellent agreement with experimental data is obtained using three different density functional approximations (one local, one general gradient and one hybrid), and our result highlights DFT as a reliable and trustworthy method for calculation and of lipophilicity for this important class of molecules. Furthermore, calculated lipophilicity results are associated with experimentally determined LD 50 and LC 50 values, showing that the most toxic pesticides are these with transient characteristics (medium lipophilicity), although this concussion must be taken with a caution due to the many factors influencing the ingestion and action of a certain substance in the body beside lipophilicity.

Carvacrol importance in veterinary and human medicine as ecologic insecticide and acaricide

Carvacrol is an active ingredient of essential oils from different plants, mainly from oregano and thyme species. It poseses biocidal activity agains many artropodes of the importance for veterinary and human medicine. Carvacrol acts as repelent, larvicide, insecticide and acaricide. It acts against pest artropodes such as those that serve as mechanical or biological vectors for many causal agents of viral, bacterial and parasitic diseases for animals and humans. Therefore, it may be used not only in pest arthropodes control but in vector borne diseases control, too. In the paper carvacrol bioactivity against mosquitoes, house flies, cockroaches, ticks and mites are described. Potencial modes of carvacrol action on artropodes are given, too. Carvacrol reachs its biotoxicity against arthropodes alone or in combination with other active ingredients from the same plant of its origin, such as tymol, cymen or others. The paper explains reasons for frequently investigations on essential oils and other natural products of plant origin to their biotoxicity against food stored pest or pest of medicinal importance, as well as, needs for their use in agriculture, veterinary and human medicine.

Involvement of cholinesterases in oxidative stress induced by chlorpyrifos in the brain of Japanese quail

&NA; Chlorpyrifos is a widely used organophosphate pesticide (OP). In birds and mammals OP exhibits a toxic effect via inhibition of cholinesterases [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)] and through oxidative/nitrosative stress. In this study, the influence of chlorpyrifos on cholinesterase activity, parameters of oxidative stress [malondialdehyde (MDA); glutathione (GSH); superoxide dismutase (SOD); nitrite concentration (NO2−); hydrogen peroxide (H2O2)], and inflammatory parameter [activity of myeloperoxidase (MPO)] in the brain of Japanese quail (Coturnix japanica) was examined. The study was conducted on a total of 60 male Japanese quails (one control and 5 experimental groups, n = 10), 3 to 4 wk old. Quails were administered by gavage chlorpyrifos (CPF) for 7 consecutive da at doses of 0.375 mg/kg BW, 0.75 mg/kg BW, 1.5 mg/kg BW, 3 mg/kg BW, and 6 mg/kg BW. Our studies have shown that all doses of CPF significantly inhibited both cholinesterases in brain: AChE from 22.74 to 37.83% and BChE from 19.53 to 61.9%, and that inhibition was dose dependent. Also, CPF has led to an increase in the concentration of MDA, GSH, NO2−, and H2O2 and activity of SOD and MPO. Overall, these results support the hypothesis that CPF causes oxidative stress and inflammatory response. This research was carried out on quails because there is hardly any or not enough data about the neurotoxic effect of CPF and especially about its influence on oxidative stress in birds. This study is highly important because we are witnessing massive avian mortality in certain countries due to pesticides.

The effect of acetylsalicylic acid and meloxicamon hematological parameters in rats

In this work there was investigated the effect of two nonsteroidal antiinflammatory drugs (NSAIDs), acetylsalicylic acid or aspirin (nonselective cyclooxygenase inhibitor - COX1 i COX2) and meloxicam (selective cyclooxygenase inhibitor - COX2) on certain hematological parameters in rats. The objective of the work was to determine whether (and to which extent), these drugs, after multiple peroral application, influence erythrocyte number, concentration of hemoglobin, hematological indices (mean corpuscular value - MCV; mean concentration of hemoglobin in erythrocytes - MCH; mean corpuscular hemoglobin concentration - MCHC), hematocrit, number of platelets, leukocytes, neutrophilic leukocytes, lymphocytes and monocytes. The experiment was conducted in in vivo conditions on 70 clinically healthy Wistar strain male rats, 10 to 12 weeks of age and body weight 250 to 300 g. The rats were divided into seven groups and they were daily perorally (by probe) given aspirin (ASCOPIR) at doses of 30, 40 and 80 mg/kg b.m. (I, II and III groups), or meloxicam (METACAM) at doses of 100, 125 and 250 μg/kg b.m. (IV, V and VI groups), for seven days. The seventh group was a control one and they were given only saline. The obtained results showed that: acetylsalicylic acid in maximum dose tested (80 mg/kg b.m.) statistically significantly reduced the number of platelets (p<0,05), the number of leukocytes (p<0,05), the number of lymphocytes (p<0,05) and the number of monocytes (p<0,05), while on the other side, meloxicam in maximum dose tested (250 μg/kg), statistically significantly reduced the mean corpuscular value (MCV), and increased the number of platelets (p<0,05), relative to the control value.

Investigations of eugenol efficacy in treatment of mange in swine

The acaricide efficacy, tolerability and safety of the active ingredient of the etheric oil of cloves eugenol was investigated in the treatment of mange in swine, and the obtained results were compared with the results of acaricide efficacy of the synthetic acaricide permethrin, which has been in use for quite a some time. A single application of permethrin in the form of a 1% solution showed maximum efficacy of 62.5%, and after three applications of 75.0% in the treatment of sarcoptes in swine mange. A single application of eugenol in the form of a 10% solution had maximum efficacy of 75.0%, and applied three times an efficacy of 100% in curbing Sarcoptes scabiei var. suis. A single administration of 20% eugenol solution showed maximum efficacy of 87.5%, and applied three times it was 100% efficient in curbing Sarcoptes scabeiei var. suis. The best efficacy in the treatment of sarcoptes mange in swine was achieved with three applications of eugenol in a concentration of 20%. This maximum effect (100%) was obtained already after the second treatment. Eugenol in a concentration of 10% was safe for local application on skin because it does not cause any undesired reactions, while a 20% concentration caused irritation followed by a passing redness and disquiet in a smaller number of treated animals. The results of comparative investigations of acaricide efficacy of permethrin and eugenol demonstrate that there is resistence in Sarcoptes scabiei var. suis to permethrin. The biocide eugenol can safely be recommended for the treatment of sarcoptes mange in swine.